This is a phase 2 randomized controlled trial to evaluate the effectiveness and toxicity of immunosuppressive drug therapy in patients with lupus membranous nephropathy. Patients with renal biopsy documented membranous nephropathy were all treated with alternate day prednisone and were randomized to receive: 1. no additional therapy (control group), 2. intravenous cyclophosphamide up to 1.0 gm per m2 body surface area every other month for 6 total doses, or 3. oral cyclosporine up to 200 mg per m2 body surface area for a total of 11 months. Patients with glomerular filtration rates 25 to 66 ml/min/1.73 m2 body surface area were randomized only to prednisone alone or to prednisone plus cyclophosphamide. Renal function and disease activity were monitored throughout the study; physiologic measures of glomerular function (glomerular filtration rate and effective renal plasma flow) were examined at study entry and at the conclusion of the study. Comparison was made of the number of favorable outcomes of glomerular function as well as drug related toxicities observed within each treatment group. Both adjunctive cyclophosphamide and cyclosporine were more effective than alternate day prednisone alone in inducing remissions of proteinuria. Relapse of high-grade proteinuria occurred significantly more often after completing cyclosporine than after cyclophosphamide. Ten patients, who were resistant to or relapsed after prednisone alone or cyclosporine, were treated with intravenous cyclophosphamide every other month for a year, followed by quarterly pulse intravenous cyclophosphamide for a median duration of 2 years. Six patients achieved a partial remission and 2 achieved a complete remission of proteinuria. We have published the analysis of the treatment outcomes as well as a detailed multivariate analysis of the demographic and clinical factors that impact the outcomes of these patients. The study remains active to facilitate additional analyses of study data and specimens.